STRINGING drug molecules into fibres that unravel in the presence of a specific enzyme could allow medication to be released exactly when and where it is needed.
Previously, drugs have been bundled with polymers that, once injected into a patient, slowly break down to release the drug. By tuning the properties of the polymer, this allows the timing of a drug鈥檚 release to be pre-programmed. However, the polymers can release toxic molecules as they degrade.
Now from the City University of New York and team have created a way to pre-program drug release without using potentially harmful polymers. In John鈥檚 system, drugs are released in response to a specific enzyme, allowing where and when the release occurs to be controlled.
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The team attached a 鈥渨ater-hating鈥� fatty acid to the end of a 鈥渨ater-loving鈥� drug molecule 鈥� in this case the painkiller paracetamol (acetaminophen). Because the water-hating fatty acid tails are attracted to each other, and the water-loving paracetamol heads to other heads, the molecules stack, with the tails at the centre and the heads facing outwards, to form nanofibres that cluster together in a mesh (see Diagram).
In the body, as long as the paracetamol is bound to the fatty acid, it is part of this mesh and is inert. But an enzyme can sever the link between the paracetamol and the fatty acid, releasing the drug. As fatty acids are naturally present in the body, there should be no harmful by-products.
The enzyme the team used to break the link is one found throughout the body. But in theory this chemical link could be tailored so that only enzymes released during a particular disease or condition can sever it.
For example, an anti-inflammatory drug could be used, with the link tweaked so that it only breaks when an enzyme released by inflamed tissue is present. This would reduce unnecessary exposure to drugs, as they would only be released where they are needed by the body.
Alternatively, a version containing chemotherapy drugs that only breaks down in response to enzymes released by tumours could be created. 鈥淚t could be applied as a gel to coat the sites of removed tumours, releasing chemotherapy drugs only if the tumour re-emerges,鈥� says co-author from the Harvard-MIT Division of Health Science and Technology. A drug could also be modified to circulate in the blood during chemotherapy treatments. As the mesh would be inert as it travelled through the bloodstream, the side effects of the drug 鈥� normally caused by it attacking healthy tissue 鈥� would be limited.
A second drug could also be trapped within the mesh: the team have added curcumin, an anti-cancer drug, to the gaps between the paracetamol fibres, using an enzyme to trigger both drugs鈥� release (Biomaterials, ). Drugs that do not have the right chemical properties to form nanofibres could be embedded in a fatty acid mesh in this way.
